Quinoline-5-carboxylic acid

Synthesis of methyl quinoline-5-carboxylate (Intermediate-97):

A 500 mL RB flask equipped with a magnetic stirrer was charged with m-aminobenzoic acid (60 g, 435 mmol), glycerol (168 g, 1824 mmol) in 90 mL of concentrated H25O4. RB flask equipped with a magnetic stirrer was charged with m-aminobenzoic acid (60 g, 435 mmol), glycerol (168 g, 1824 mmol), 3-nitrobenzoic acid (30 g, 179 mmol) in 90 mL of concentrated H25O4. The reaction mixture was heated at 150 ??C for 7 h. After the reaction was cooled to room temperature MeOH (600 mL) was added and refluxed for 12 hours. It was then cooled to 0??C, burst with ice and concentrated. The crude reaction mixture was alkalized with NaHCO3, extracted with DCM and concentrated. The resulting crude material was purified by silica gel column chromatography using petroleum ether (60-80), ethyl acetate and 0.5% triethylamine as eluents. A product (Intermediate-97) was obtained as a brown liquid (21 g).

Synthesis of quinoline-5-carboxylic acid (Intermediate-98):

To a stirred solution of Intermediate-97 (21 g, 112 mmol) in THF:MeOH mixture (25 mL:200 mL) at 0 ??C, LiOH (10.75 g, 448 mmol) in water (25 mL) was added. The resulting reaction mixture was stirred at room temperature for 3 hours. After the reaction (monitored by TLC), it was concentrated and acidified with 1N.HCl (pH = 5). The resulting precipitate was filtered and dried to yield intermediate-98 (19 g).